Molecular and immunohistochemical techniques provide insights that will allow us to tailor the management of patients with breast cancer. BRCA1 is becoming an important prognostic factor for breast cancer. The morphological features of tumors from patients with breast cancer associated with BRCA1 mutation include higher grade, with an excess of medullary carcinoma (Marcus et al., 1996). Tumors associated with BRCA1 mutation are more likely to be steroid hormone receptor (ER and PR) negative (Osin et al., 1998). The present study showed an alteration in BRCA1 mRNA expression in 40% of tissues studied, with a statistically significant relationship between BRCA1 mRNA expression and poor prognosis as well as high-tumor grade (P<0.05). This finding is consistent with a study demonstrating that alteration in BRCA1 gene expression significantly correlates with higher breast cancer histological grade (Lee, 2002). Grade is an independent prognostic indicator and is inversely related to outcome (Elston and Ellis, 1991). Several reports have indicated that a specific histopathological phenotype can be recognized in breast carcinoma occurring in women with germline mutations in BRCA1 (Elston and Ellis, 1991; Stratton, 1997). One of these studies reported an increased rate of ductal carcinoma in breast cancers associated with BRCA1 mutations (Elston and Ellis, 1991). Others reported an increase in the incidence of tumors with a medullary and atypical medullary pattern within the group of ductal carcinomas associated with BRCA1 mutations (Marcus et al., 1996; Stratton, 1997). The findings of the present study support the findings of these workers. However, 40% of breast cancers with alteration in BRCA1 mRNA in the study were mainly high-grade carcinoma. Moreover, this study showed an association between BRCA1 expression and negative ER and PR expression (statistically significant). Previous reports also showed that breast cancers associated with BRCA1 mutation were significantly more often ER and PR negative (Marcus et al., 1996; Lakhani et al., 2002). ER has become one of the most important prognostic and predictive markers for breast cancer (Lakhani et al., 2002). ER-positive tumors tend to grow more slowly, are better differentiated, and are associated with slightly better overall prognosis (Karp et al., 1997). PR status is also a good predictor of tumor responsiveness to therapy. Approximately 75% of ER/PR-positive tumors respond positively to endocrine therapy (Clark, 2000; Elledge and Fuqua, 2000). In addition to the above relationship with hormone receptors, the present study also demonstrated a positive relationship between overexpression of the protooncogene HER-2 in breast cancers with alteration of BRCA1 mRNA (33% of cases), one of which was CK5/6 positive. Our findings are in agreement with the study by Yoshikawa et al. (1999), who reported that breast cancers with reduced BRCA1 protein expression had a tendency toward overexpression of HER-2. This protooncogene is a biological marker for breast cancer, overexpression of which indicates poor prognosis. Furthermore, HER-2 is amplified in ∼20% of invasive cancers and has received interest because of its association with lymph node metastasis and its short relapse time, poor survival, and decreased response to endocrine and chemotherapy (Varley et al., 1987). Antibodies directed against the HER-2 protein have attracted a lot of attention because of the availability of the monoclonal antibody Herceptin for treatment of breast cancer (Slamon et al., 2001). Some studies have reported that breast cancers associated with BRCA1 mutations develop at a relatively early age (Elston and Ellis, 1991). Women carrying a BRCA1 or BRCA2 mutation are known to have an increased risk of developing contralateral primary breast cancer (Metcalfe et al., 2004), which is even more apparent among younger (age <50 years) women diagnosed with a primary breast carcinoma (Robson et al., 1998; Verhoog et al., 2000). In another study, a BRCA1 mutation carrier presented with metastatic disease 3.5 years after prophylactic mastectomy (no primary breast cancer found), suggesting the presence of an occult primary tumor that was never found, despite a thorough reexamination of the specimen at the time of presentation with the metastatic disease. This finding emphasizes the fact that, despite thorough examination of the mastectomy specimens, the presence of an occult breast cancer cannot be ruled out completely and indicates that a form of surveillance after prophylactic mastectomy might be relevant (Meijers-Heijboer et al., 2001). BRCA1 or BRCA2 mutation carriers and women from a hereditary breast/ovarian cancer family have a highly increased risk of developing breast cancer. Prophylactic mastectomy results in the greatest reduction in breast cancer risk (Heemskerk-Gerritsen et al., 2007).
There are no conflicts of interest.
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